Our present view of the pathway of carnitine biosynthesis from lysine based principally on radioisotope dilution and incorporation experiments is as follows: Lysine (LYS) yields epsilon-N- monomethyllysine (MML) yields epsilon-N-dimethyllysine (DML) yields epsilon-N-trimethyllysine (TML) yields gamma-butyrobetaine (gamma-BB) yiels carnitine (CARN). Efforts will continue to purify an S-adenosylmethionine dependent enzyme from Neurospora that methylates DML forming TML but is less active toward MML and LYS. Details of the DML yields TML conversion will be studied and efforts made to discorer the conditions necessary for th methylation of LYS and MML relative to the CARN pathway. Kidney homogenates readily form gamma-BB from TML. Conditions will be sought that favor accumulation of intermediates to permit their isolation and idetification, thus shedding light on the nature of the TML yields gamma-BB transformation. Oxidation of 1-C14 palmitate by heart mitochondrial preparations and heart homogenates from LYS-CARN deficient rats in an effort to demonstrate thad a CARN deficiency induced by consumption of a diet limiting in LYS results in an impairment in lipid oxidation have only been suggestive to date. Such studies are continuing under more stringent dietary conditions.